The standard of care in peripheral nerve repair is microsuturing of the nerve. This procedure reconnects the proximal and distal ends of the nerve by placing sutures in the epineurial sheath, a wrapper of connective tissue, that surrounds the nerve.
The quality of recovery from a repaired injured nerve varies from patient to patient. However, both the speed with which function and sensation return to the nerve and quality of the recovery are directly proportional to the distance from the injury to the end of the appendage. Injuries to the fingers routinely reach 40-50% of normal function within 3-6 months. Injuries to the brachial plexus (armpit area) may only reach 0-20% of normal function and take 2-3 years to achieve even this poor return of function and sensation.
The neurons below the site of injury degenerate because they are no longer connected to the cell nucleus, which for peripheral nerves are located near the spinal column.
The quality of recovery from a repaired injured nerve is measured by several methods. Functional testing of sensation, sensibility and strength are commonly used. However, as different parts of the body vary in form and function, the most consistent measurements across body regions assess sensation and sensibility. All are noninvasive. The methods of assessment are standardized, routine and quantitative.
Known for over 150 years, degeneration of the distal portion of a nerve after injury is a well understood process. After a few days from injury, the distal axons within a severed or crushed mammalian nerve always undergo degeneration. Specifically, the axons die and inflammatory cells remove the debris. This is presumed to be due to broken communication with the cell body of the neuron.
Suturing a severed nerve is actually suturing the outside of the nerve together. This connects the proximal and distal connective tissue wrappers of the nerve, the epineurium. The axons within a severed nerve do not reconnect when sutured.
At present there are no known technologies in development that can result in fusion of the axons within an injured peripheral nerve.
Single cut injuries to a peripheral nerve are defined as a cut that, when trimmed and prepared for suturing, has a gap between the proximal and distal ends of the nerve as measured across the injury lesion of less than 1.5mm.
Preclinical data suggest that Wallerian degeneration becomes irreversible after ~72 hours from the injury. PEG-fusion within this timeframe has been shown to be effective. Clinical data suggests this period can be extended to as many as 10 days with the use of immunosuppresors such as cyclosporin, however this is not currently being explored in clinical studies of AxoFuse®.
An autograft is when the donor and recipient are the same person/animal. An allograft is when the donor and the recipient are different persons/animals of the same species.
A loss of a segment of a nerve either as a crush event or due to a laceration with a wide blade is termed a segmental ablation.
There is actually no difference in the way the PEG-fusion method works for single cut and for segmental ablations. The difference for an ablation is that two procedures are necessary to PEG-fuse a segment of nerve from a donor into the gap in the recipient’s nerve.
This question has not yet been studied. Current data already shows that engrafted nerve segments for gap injuries as large as 10mm can be successfully PEG-fused. Based on preclinical studies it is likely that very long segments can be successfully PEG-fused. Neurpative intends to develop AxoFuse® for 1.5mm - 75mm gap autograft repairs.
Possibly, however there are several limitations to the PEG-fusion technique in the spine. Importantly, it is very infrequent for a spinal cord injury to consist of a severed cord. Instead, most spinal cord injuries are crush injuries and are also generally very traumatic. Also, the requirement for the proximal and distal ends of a severed nerve be placed in very close approximation, a currently unsolved problem for spinal cord repair.